A productive infection by vaccinia virus involves entry into the cell; expression and replication of the genome; defense against specific and non-specific host immune mechanisms; and assembly and release of infectious, enveloped, virus particles. Many of these steps involve interactions of viral proteins with cellular proteins or membranes. Combined genetic, biochemical, and electron microscopic approaches are being used to investigate these complex processes. During the past year, emphasis has been on understanding the steps in the formation and transmission of extracellular virions. We found that three viral proteins: A33, A34, and A36 are required to form actin tails on intracellular virus particles. When actin tails do not form, specialized microvilli are not detected and the cell-to-cell spread of vaccinia virus is inefficient